Search Results (11)

Objectives: Persistent Human Papillomavirus (HPV) infection in the cervix and the preinvasive lesions it causes are significant risk factors for cervical cancer. Therefore, a treatment strategy is necessary to facilitate the clearance of HPV and prevent the progression of preinvasive lesions without causing cervical tissue destruction. This study aimed to evaluate the effectiveness of a vaginal adsorbent gel composed of a hydroxyethyl cellulose matrix formulation containing dispersed silicon dioxide, antioxidant sodium selenite, deflamin, and citric acid in patients with HPV infection. Methods: The study was designed as a retrospective cohort study and involved 449 women infected with HPV. For the purposes of the study, the patients were divided into two groups: the treatment group (TG) comprised 207 patients who used the vaginal gel daily for a period of three months, while the control group (CG), consisting of 242 patients, received no treatment under an “active surveillance” protocol. The study’s endpoints encompassed the domains of cytology, histology, and HPV clearance. Results: The regression rate of smear pathologies was 24.8% in the control group and 29.0% in the group using the vaginal adsorbent gel. In the first year, the histological regression rate in cervical biopsies was 49.3% in the treatment group and 19.4% in the control group, with a significant difference between groups (p < 0.001). Moreover, the clearance rate of HPV types was found to be significantly higher in the group using the vaginal adsorbent gel. Conclusions: The findings of this study suggest that the outpatient treatment approach can effectively prevent the oncogenic progression of cervical dysplasia. This alternative method has been shown to be efficacious in preventing the progression of cervical dysplasia and promoting regression. Furthermore, the efficacy of this gel in eradicating HPV has been demonstrated within a 12-month period. Full article

Background: Cervical cancer continues to pose a significant global health challenge, particularly in low-resource regions with limited access to advanced diagnostics. Cervical conization can occasionally uncover invasive carcinoma in patients initially suspected of having only pre-invasive lesions. This study assessed the platelet-to-lymphocyte ratio (PLR) as a potential predictive biomarker for identifying invasive disease in patients undergoing a loop electrosurgical excision procedure (LEEP). Methods: A retrospective study was conducted on 371 patients who underwent LEEP conization for cervical dysplasia. Preoperative PLR values were collected and compared across final histopathological categories (negative, low-grade, high-grade, invasive carcinoma) using the Kruskal–Wallis test, followed by Mann–Whitney U tests for pairwise comparisons. Receiver operating characteristic (ROC) analysis was used to evaluate diagnostic accuracy. Results: PLR values above 7.7 were significantly associated with HPV positivity, increasing with histopathological severity. There were significant PLR differences across the outcome groups (p = 0.005), with notably higher values in cases of invasive carcinoma (p < 0.01). ROC analysis showed moderate diagnostic utility (AUC ≈ 0.72); at a PLR cutoff of ~11.9, sensitivity was 65% and specificity 81%. Conclusions: The PLR cutoff of 7.7 was associated with HPV positivity, while a higher cutoff of 11.93 was identified for predicting invasive cervical cancer. These findings support that preoperative PLR is a non-invasive, clinically relevant marker correlated with lesion severity, offering potential for preoperative risk stratification, particularly where advanced diagnostics are limited. Full article

In this comprehensive review supported by clinical examples, the authors explore the topic of cervical cancer in pregnancy, with emphasis on potential pre-cancer progression, the possibility of coexisting preinvasive and invasive disease, and neoadjuvant chemotherapy. This manuscript addresses the challenges of managing cervical cancer in pregnant women with a pregnancy-preserving approach, including the importance of screening, the timing of surgery, and the impact of pregnancy on the course of the disease. The first case study illustrates the potential for a benign cervical lesion to transform into a malignant one during pregnancy and the possible coexistence of preinvasive lesions together with early-stage cervical cancer. It also questions the rationale behind the non-treatment of pregnant patients initially diagnosed with CIN 2/3 during pregnancy. The second presented clinical example shows the histologically confirmed response to neoadjuvant chemotherapy, resulting in a radiologically diagnosed FIGO stage IIA1 being downgraded to adenocarcinoma in situ in the histology report after surgery performed six weeks postpartum. The treatment of cervical cancer, which is becoming increasingly prevalent among pregnant women, and the necessity for an individualized diagnostic and therapeutic approach represent significant challenges for contemporary medicine. Discrepancies in therapeutic options proposed among centers within the same region lead to the conclusion that there is a need for centralization and unification of evidence-based management in referral centers with both high-level oncological and perinatal care. Full article

Background and Objectives: Cervical cancer (CC) represents a significant health concern worldwide, particularly for younger women. Cold knife (CK) conization and carbon dioxide (CO₂) laser conization are two techniques commonly used to remove pre-invasive lesions, offering a potential curative intent in cases of incidental diagnosis of CC. This study aimed to assess the clinical implications and pathological outcomes of CK vs. CO₂ laser conization for pre-invasive lesions. Materials and Methods: We retrospectively analyzed women who underwent CO₂ or CK conization for high-grade preinvasive lesions (CIN2/3, CIS and AIS) between 2010 and 2022. Patient demographics, surgical details and pathological outcomes were collected. Pregnancy outcomes, including composite adverse obstetric rates, and oncological follow-up data, were also obtained. Results: In all, 1270 women were included; of them, 1225 (96.5%) underwent CO₂, and 45 (3.5%) underwent CK conization. Overall, the rate of positive endocervical or deep margins was lower with CO₂ laser compared to CK (4.3% vs. 13.3%, p = 0.015). Incidental CC was diagnosed in 56 (4.4%) patients, with 35 (62.5%) squamous and 21 (46.6%) adenocarcinomas. In a multivariate regression model, the relative risk for positive endocervical or deep margins is significantly greater in cases of incidental diagnosis of CC (p < 0.01). In cases of incidental diagnosis of CC, we found that the probabilities of having either positive endocervical or deep margins after CO₂ laser or CK conization are similar, with a higher risk in case of adenocarcinoma lesion. Among women with CC, 42 (75%) opted for radical treatment, while 14 (25%) underwent a follow-up. Only one woman (7.1%) in the follow-up group, who had undergone CK conization, experienced a composite adverse obstetric outcome. No recurrences were observed after a median follow-up of 53 months. Conclusions: CO₂ laser conization achieved a lower positive margin rate overall. CK and CO₂ conization appear to be equivalent oncological options for incidental CC. Full article

Background. Neurotrophins, such as BDNF and NGF, are overexpressed in tumor cells in cervical cancer, and HIV infection is associated with the upregulation of neurotrophin expression. Therefore, we aimed to investigate whether BDNF and NGF are overexpressed in preneoplastic cervical disease from HIV-infected women. Methods. Women with preneoplastic cervical lesions (cervical intraepithelial neoplasia grade 2 or 3) were prospectively enrolled and grouped according to their HIV status. Samples from Loop Electrosurgical Excision Procedure (LEEP) for suspected cervical cancer were obtained, and immunohistochemistry was performed to evaluate BDNF and NGF expression. Results. We included in our analysis 12 HIV-infected patients who were matched with 23 HIV-negative patients as a control group. Immunohistochemistry analysis showed that BDNF expression was significantly higher in cervical preneoplastic lesions from HIV-positive women than in the lesions from the control group. In particular, BDNF was expressed in 8/12 HIV-positive patients and 7/23 HIV-negative patients (66.7% vs. 30.4%, χ² = 4.227; p = 0.040). NGF expression was not significantly higher in cervical preneoplastic lesions from HIV-positive women compared with that in the lesions from the control group. In particular, NGF was expressed in 8/12 HIV-positive patients and in 12/23 HIV-negative patients (66.7% vs. 52.2% χ² = 0.676; p = 0.411). Logistic regression analysis showed that the HIV status is an independent predictor of BDNF expression in pre-invasive preneoplastic cervical disease when considered alone (crude OR 4.6, 95% CI 0.027–20.347; p = 0.046) and when analyzed with other co-factors (adjusted OR 6.786, 95% CI 1.084–42.476; p = 0.041). Conclusions. In preneoplastic cervical disease, BDNF expression is higher in HIV-infected women than in non-infected controls, and this is independent of the clinical features of the patients and from the presence of the HPV-HR genotype. BDNF can play a key role as a link between the pathways by which HIV and HPV interact to accelerate cervical cancer progression and invasion. These data can be useful to better understand the role of neurotrophins in the cancerogenesis of cervical cancer and the possible therapeutic strategies to improve disease outcomes. Full article

Triage methods for cervical cancer detection show moderate accuracy and present considerable false-negative and false-positive result rates. A complementary diagnostic parameter could help improve the accuracy of identifying patients who need treatment. A pilot study was performed using a targeted proteomics approach with opportunistic ThinPrep samples obtained from women collected at the hospital’s outpatient clinic to determine the concentration levels of minichromosome maintenance-3 (MCM3) and envoplakin (EVPL) proteins. Forty samples with ‘negative for intraepithelial lesion or malignancy’ (NILM), 21 samples with ‘atypical squamous cells of undetermined significance’ (ASC-US), and 33 samples with ‘low-grade squamous intraepithelial lesion and worse’ (≥LSIL) were analyzed, using cytology and the patients’ histology reports. Highly accurate concordance was obtained for gold-standard-confirmed samples, demonstrating that the MCM3/EVPL ratio can discriminate between non-dysplastic and dysplastic samples. On that account, we propose that MCM3 and EVPL are promising candidate protein biomarkers for population-based cervical cancer screening. Full article

Background: High-risk HPV infection is responsible for >99% of cervix cancers (CC). In persistent infections that lead to cancer, the tumour breaches the basement membrane, releasing HPV-DNA into the bloodstream (cHPV-DNA). A next-generation sequencing assay (NGS) for detection of plasma HPV circulating DNA (cHPV-DNA) has demonstrated high sensitivity and specificity in patients with locally advanced cervix cancers. We hypothesised that cHPV-DNA is detectable in early invasive cervical cancers but not in pre-invasive lesions (CIN). Methods: Blood samples were collected from patients with CIN (n = 52) and FIGO stage 1A-1B CC (n = 12) prior to treatment and at follow-up. DNA extraction from plasma, followed by NGS, was used for the detection of cHPV-DNA. Results: None of the patients with pre-invasive lesions were positive for CHPV-DNA. In invasive tumours, plasma from one patient (10%) reached the threshold of positivity for cHPV-DNA in plasma. Conclusion: Low detection of cHPV-DNA in early CC may be explained by small tumour size, poorer access to lymphatics and circulation, and therefore little shedding of cHPV-DNA in plasma at detectable levels. The detection rate of cHPV-DNA in patients with early invasive cervix cancer using even the most sensitive of currently available technologies lacks adequate sensitivity for clinical utility. Full article

(1) Purpose: To investigate the efficacy and safety of using PDT in the treatment of severe intraepithelial squamous lesions of the cervix and preinvasive cervical cancer associated with HPV in women of reproductive age. (2) Methods: The examination and treatment of 45 patients aged 22–49 years with morphologically confirmed HPV-associated cervical intraepithelial neoplasia of a severe degree (17 patients) and preinvasive cervical cancer (28 patients) were performed. All patients underwent PDT of the cervix using a chlorin e6 photosensitizer; after which, the affected areas of the cervix were evaluated using video and spectral fluorescence diagnostics. PDT effectiveness was assessed on the basis of colposcopy data, a cytological examination of exo- and endocervix and PAP test scrapings or the liquid cytology method, and polymerase chain reaction for HPV carriage 4 weeks after PDT, as well as on the basis of histological and immunohistochemical studies of biopsy materials 5 weeks after PDT. The expression levels of the Ki-67 and p16 markers in the affected areas of the cervix were also assessed. (3) Results. All patients included in the study tolerated the intravenous administration of the photosensitizer well, with no side effects or allergic reactions observed. In 88.2% of patients with CIN III/HSIL and in 85.7% of women with preinvasive cervical cancer, the effect of the treatment was noted after the first PDT procedure, while complete regression of the dysplasia foci was observed in 15 women (88.2%) with CIN III/HSIL and in 25 patients (89.3%) with preinvasive cervical cancer. Partial regression to the form of LSIL/CIN I was noted in two cases (11.8%) in the CIN III/HSIL group and in three cases (10.7%) in the group of patients with preinvasive cervical cancer. After PDT, a statistically significant decrease in the expression of the Ki-67 and p16 levels relative to the initial values was noted. (4) Conclusions. The results obtained indicate the high efficiency of PDT with intravenous administration of the chlorin photosensitizer for the treatment of intraepithelial lesions of the cervix with a selective effect on pathologically altered tissue. The use of this approach makes it possible to preserve the normal anatomical and functional characteristics of the cervix, which is especially important for maintaining the fertility of patients. Full article

The screening for pre-invasive cervical lesions has significantly decreased the incidence of cervical neoplasm. It is recommended to be performed starting with the age of 21 with a frequency of 3–5 years and it consists of pap smear testing and HPV genotyping, and, if required, it can be continued with colposcopy or biopsy followed by pathological assessment. The importance of the early diagnosis of pre-invasive cervical lesions has led to several studies on this topic. The paper analyzed the modern literature published on the PubMed and Scopus databases. Reference studies have found that most intraepithelial lesions are caused by the presence of HPV. Other commonly associated factors are immunosuppression, multiparity and other viral infections. HPV infection can be prevented by vaccination. It is recommended for people between 11 and 26 years old and also over 27 years old if they associate risk factors. A meta-analysis performed on patients diagnosed with CIN2 revealed a lower recurrence rate in vaccinated women than in unvaccinated women. Other studies have shown the transient nature of HPV infection and spontaneous regression of pre-invasive lesions. The early diagnosis of pre-invasive lesions is necessary for the initiation of therapeutic and follow-up behavior as soon as possible, with the aim of reducing the incidence of cervical cancer. This is possible and easy to access through national health programs. Full article

The establishment of a proangiogenic phenotype and epithelial-to-mesenchymal transition (EMT) are considered as critical events that promote the induction of invasive growth in epithelial tumors, and stimulation of lymphangiogenesis is believed to confer the capacity for early dissemination to cancer cells. Recent research has revealed substantial interdependence between these processes at the molecular level as they rely on common signaling networks. Of great interest are the molecular mechanisms of (lymph-)angiogenesis and EMT associated with the earliest stages of transition from intraepithelial development to invasive growth, as they could provide the source of potentially valuable tools for targeting tumor metastasis. However, in the case of early-stage cervical cancer, the players of (lymph-)angiogenesis and EMT processes still remain substantially uncharacterized. In this study, we used RNA sequencing to compare transcriptomes of HPV(+) preinvasive neoplastic lesions and early-stage invasive carcinoma of the cervix and to identify (lymph-)angiogenesis- and EMT-related genes and pathways that may underlie early acquisition of invasive phenotype and metastatic properties by cervical cancer cells. Second, we applied flow cytometric analysis to evaluate the expression of three key lymphangiogenesis/EMT markers (VEGFR3, MET, and SLUG) in epithelial cells derived from enzymatically treated tissue specimens. Overall, among 201 differentially expressed genes, a considerable number of (lymph-)angiogenesis and EMT regulatory factors were identified, including genes encoding cytokines, growth factor receptors, transcription factors, and adhesion molecules. Pathway analysis confirmed enrichment for angiogenesis, epithelial differentiation, and cell guidance pathways at transition from intraepithelial neoplasia to invasive carcinoma and suggested immune-regulatory/inflammatory pathways to be implicated in initiation of invasive growth of cervical cancer. Flow cytometry showed cell phenotype-specific expression pattern for VEGFR3, MET, and SLUG and revealed correlation with the amount of tumor-infiltrating lymphocytes at the early stages of cervical cancer progression. Taken together, these results extend our understanding of driving forces of angiogenesis and metastasis in HPV-associated cervical cancer and may be useful for developing new treatments. Full article

Background: Cervical cancer (cca) is largely a preventable disease if women receive regular screening, which allows for the detection and treatment of preinvasive lesions before they become invasive. Having been inadequately screened is a common finding among women who develop cca. Our primary objective was to determine the Pap screening histories of women diagnosed with cca in Montreal, Quebec. Secondary objectives were to determine the characteristics of women at greatest risk of cca and to characterize the level of physician contact those women had before developing cca. Methods: The Invasive Cervical Cancer Study, a population-based case–control study, consisted of Greater Montreal residents diagnosed with histologically confirmed cca between 1998 and 2004. Respondents to the 2003 Canadian Community Health Survey and a sample of women without cca obtained from Quebec medical billing records served as controls. Results: During the period of interest, 568 women were diagnosed with cca. Immigrants and women speaking neither French nor English were at greatest risk of cca. Most of the women in the case group had been screened at least once during their lifetime (84.8%–90.4%), but they were less likely to have been screened within 3 years of diagnosis. Having received care from a family physician or a medical specialist other than a gynecologist within the 5 years before diagnosis was associated with a greater risk of cca development. Conclusions: Our findings provide evidence of the need for an organized population-based screening program. They also underscore the need for provider education to prevent missed opportunities for cca screening when at-risk women seek medical attention. Full article